Genetic Susceptibility to Eating Disorders: Associated Polymorphisms and Pharmacogenetic Suggestions

Abstract

Anorexia nervosa (AN), bulimia nervosa (BN) and binge-eating disorder (BED) are characterized by abnormal eating behaviors often resulting in dramatic physical consequences for the patients. The etiology of eating disorders (EDs) is currently unknown; however, a strong genetic contribution is likely to be involved. To date, the majority of genetic studies have focused on candidate genes, and polymorphic variants of genes coding for substances likely to be involved in the etiopathogenesis of EDs have been assessed for association with AN, BN, BED and/or ED-related phenotypic traits. Results have been generally inconsistent and cannot be considered conclusive because of several methodological flaws and differences, such as small sample sizes, ethnic heterogeneity of studied populations, lack of statistical correction for multiple testing, adoption of different diagnostic criteria and population stratification. Although, at present, no convincing evidence for associations of candidate genes with EDs has been provided, the 5-HT(2A) receptor gene and the BDNF gene seem to be promising candidates for genetic influences on AN, since polymorphic variants of these genes have been found quite consistently, although not specifically, linked to AN restricting subtype in large sample studies. Moreover, pharmacogenetic investigations have suggested a possible role of some gene polymorphisms in predicting the response to treatment with selective serotonin reuptake inhibitors in BN, but results are still preliminary. The heterogeneity of ED phenotypes is believed to represent the most relevant variable responsible for contradictory and not conclusive results. Future studies should focus on more homogeneous subgroups, either relying on specific ED traits or identifying endophenotypes. This will be useful also for prevention and treatment of EDs.

The 5‐HTTLPR polymorphism and eating disorders: A meta‐analysis

“…There is a growing evidence that eating disorders are influenced not only by environmental factors but also by genes of several systems 2,3 : serotonin candidates (serotonin transporter, serotonin receptors 5-HT2A, 5-HT2C, 5-HT1Db, and 5-HT7, tryptophan hydroxylase 1), dopamine candidates (dopamine transporter 1, dopamine receptors DRD2, DRD3, DRD4), noradrenaline candidates (noradrenaline transporter, b3-adrenergic receptor), monoamine-degrading enzyme genes (catechol-O-methyltransferase, monoamine oxidase A), central regulators of feeding and peripheral regulators of feeding genes.…”

“…4,5 The gene coding for the serotonin transporter (5-HTT or SERT) has been suggested as a good candidate for genetic studies on eating disorders. 2 The 5-HTT is an integral membrane protein localized in presynaptic neuronal membranes. It acts taking up serotonin into the presynaptic neurons after its release in the synaptic cleft, with the purpose of terminating serotonin action and recycling it.…”

Genetic aspects of binge eating disorder Part 2. Molecular genetics and pharmacogenetic approaches

“…При обследовании японской популя-ции [30] было установлено, что аллель G полиморфизма MspI (-1438A/G) в промоторном регионе гена 5HT2A ре-цептора увеличивает риск приступообразного переедания в рамках булимии и коморбидных пограничных психиче-ских расстройств. При этом ряд полиморфизмов в генах Журнал неврологии и психиатрии, 8,2016 генетика приступооБразного переедания 5-HT2A рецептора и BDNF обнаружил связь с анорексией [31]. Не выявлено влияния полиморфизма в кодирующей части (cys23ser) гена 5-HT2C рецептора на риск развития булимии и ВЕD у женщин [32].…”

“…СИОЗС оказались достаточно эффективными при лече-нии булимии и BED. Однако соответствующие результа-ты носят предварительный характер [31]. Как правило, фармакотерапия используется в комплексе с психотера-пией и психологическим консультированием, и в целом их комбинации более эффективна, чем только фармако-терапия [55], причем есть точка зрения [56], что эффект психотерапии также контролируется генетически через влияние на черты личности.…”

Epigenetic Mechanisms on Food Addiction

“…Both addictive drugs and palatable foodstuffs exposure produce neuro-adaptations (e.g., a repeated stimulation of mesolimbic DA-ergic neurotransmission) that lead to compulsive drug-and food-seeking behavior [9,11,12]. Moreover, several studies found an implication of genes involved in weight regulation, eating behavior, mood, and stress responsivity [9,13]. Genetic variants in eating disorders have been investigated [14][15][16], and the Taq1A (minor) allele of DA receptors D2 (DRD2) gene is associated with many of substance-misuse disorders [16][17][18].…”